CN102085376A - Phospholipid complex of gentian total glucosides and preparation method thereof - Google Patents
Phospholipid complex of gentian total glucosides and preparation method thereof Download PDFInfo
- Publication number
- CN102085376A CN102085376A CN2009102001169A CN200910200116A CN102085376A CN 102085376 A CN102085376 A CN 102085376A CN 2009102001169 A CN2009102001169 A CN 2009102001169A CN 200910200116 A CN200910200116 A CN 200910200116A CN 102085376 A CN102085376 A CN 102085376A
- Authority
- CN
- China
- Prior art keywords
- total glucosides
- radix gentianae
- phospholipid
- gentianae total
- phosphatide complexes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of Chinese medicament pharmacy, and relates to a phospholipid complex of gentian total glucosides serving as a Chinese medicinal effective site and a preparation method thereof. The phospholipid complex consists of the gentian total glucosides, soya bean lecithin and yolk lecithin or synthesized phospholipid in a molar ratio of 1:10-15:1, and is prepared by heating reflux, washing and drying. The phospholipid complex is formed by the gentian total glucosides and a certain amount of phospholipid in a proper solvent, so the physicochemical property of the gentian total glucosides is changed, the lipid solubility and the stability of the gentian total glucosides are enhanced, the transport performance of the gentian total glucosides across membranes is improved, and the bioavailability of the gentian total glucosides is improved. The preparation method has simple process and good reproducibility, and is suitable for industrialized production.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, be specifically related to phosphatide complexes of a kind of effective ingredient in Chinese Radix Gentianae total glucosides and preparation method thereof.
Background technology
Radix Gentianae total glucosides is the water solublity secoiridoid glycoside effective site that separation and purification obtains in conventional Chinese medicine material Radix Gentianae (Radix Et Rhizoma Gentianae) and the Radix Gentianae Macrophyllae (RadixGentianae Macrophyllae), its effective ingredient comprise gentiopicrin, sweroside, sweroside, bitter Radix Gentianae ester glycosides, bitter when medicine ester glycosides etc., wherein the highest with Determination of gentiopicroside, activity is the strongest." Chinese pharmacopoeia (version in 2005) is promptly with the quantitative target of gentiopicrin as Radix Gentianae and gentiana macrophylla medicine.Figure below is the structural formula of Radix Gentianae total glucosides.Studies show that gentiopicrin has significant anti-liver injury, antiviral, antiinflammatory action, have important exploitation and be worth.But because the gentiopicrin water solublity is strong, the transmembrane transport poor performance is difficult to see through gastrointestinal wall and is absorbed and enters the body circulation; And in gastrointestinal tract the character instability, easily be degraded, cause bioavailability very low.There are some researches show that the absolute bioavailability behind the oral gentiopicrin of Beagle dog only is 4.20%.Cross low bioavailability, influenced the performance of Radix Gentianae total glucosides oral formulations curative effect, limited its use clinically.
Phosphatide complexes (phytosome or phospholipid complex) means in non-proton carrier series solvent, medicine combines with certain proportion relation with phospholipid and the complex that forms, be at first to discover, in aprotic solvent, form by Van der Waals force or hydrogen bonded by medicine and phospholipid by Italian scholar Bombardelli etc.Phospholipid is the important component part of cell membrane, its molecular structure is made up of polar head and nonpolar amphipathic afterbody, owing to having the strong electronics that gets, oxygen atom in the hydroxyl on the phosphorus atoms in the phospholipid is inclined to, nitrogen-atoms has strong betatopic tendency, therefore under certain condition, can with the compound generation complex of the medicine of a fixed structure.And because phospholipid molecule amphipathic, also be very effective emulsifying agent.After active skull cap components and phospholipids incorporate form complex, usually show and remarkable different physicochemical property and the biological natures of former chemical compound, can improve the fat-soluble and stable of water soluble drug significantly, improve its transmembrane transport performance, and then improve bioavailability of medicament; Have the release of delaying simultaneously, reduce advantages such as body internal diabetes removal rates.Therefore, phosphatide complexes is considered to improve a kind of effective means of Chinese medicine water soluble ingredient oral administration biaavailability.
Summary of the invention
The purpose of this invention is to provide phosphatide complexes of a kind of effective ingredient in Chinese Radix Gentianae total glucosides and preparation method thereof.This phosphatide complexes can improve the fat-soluble of Radix Gentianae total glucosides and transmembrane transport performance, increases its oral administration biaavailability, strengthens its pharmacologically active.
It is crude drug that the present invention adopts water solublity effective ingredient in Chinese Radix Gentianae total glucosides, adopts suitable preparation method to make the Radix Gentianae total glucosides phosphatide complexes with phospholipid; Or make peroral dosage forms such as tablet, capsule behind the adding sorptive material.
Phosphatide complexes of the present invention was made up of Radix Gentianae total glucosides and soybean lecithin, Ovum Gallus domesticus Flavus lecithin or synthetic phospholipid in 1: 10 in molar ratio～15: 1, formed through reflux, washing drying.The present invention is by forming phosphatide complexes with Radix Gentianae total glucosides and a certain amount of phospholipid in suitable solvent, thereby changes the physicochemical property of Radix Gentianae total glucosides, strengthens its fat-soluble and stability, improves its transmembrane transport performance, thereby improves its bioavailability.Preparation technology of the present invention is simple, favorable reproducibility, is fit to suitability for industrialized production.
Radix Gentianae total glucosides of the present invention is meant that with Chinese crude drug Radix Gentianae or Radix Gentianae Macrophyllae be raw material, through extracting the water solublity effective site that purification obtains, wherein adopt determined by ultraviolet spectrophotometry, must not be lower than 50% in the content of the Radix Gentianae total glucosides of gentiopicrin, adopt the Determination of gentiopicroside of high effective liquid chromatography for measuring must not be lower than 20%.
Phospholipid of the present invention is that natural phospholipid or synthetic phospholipid or natural phospholipid mix use with synthetic phospholipid.Wherein natural phospholipid is selected from soybean lecithin or Ovum Gallus domesticus Flavus lecithin; Synthetic phospholipid is selected from hydrogenated soy phosphatidyl choline, hydrogenated yolk lecithin, dipalmitoyl phosphatidyl choline, two palmityl PHOSPHATIDYL ETHANOLAMINE, distearoyl phosphatidylcholine or DSPE.Can be wherein a kind of independent use, also can be that two or more mixes use.Preferably soya lecithin wherein.
The preparation method of Radix Gentianae total glucosides phosphatide complexes of the present invention is: take by weighing an amount of Radix Gentianae total glucosides and phospholipid in molar ratio, join in the suitable organic solvent, under the uniform temperature condition, behind the reaction certain hour, organic solvent is removed in decompression or lyophilization, add atent solvent again and separate not compound free drug, remove atent solvent, drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes of the present invention, wherein the mol ratio of Radix Gentianae total glucosides and phospholipid is 1: 10～15: 1.Preferred proportion is 1: 5～5: 1.
The organic solvent that adopts in the phosphatide complexes preparation process of the present invention can be selected normal hexane, oxolane, methanol, ethanol, cyclohexane extraction, dioxy cyclohexane extraction, dichloromethane, ethyl acetate, chloroform, ether, acetone, n-butyl alcohol, dioxy six alkane, butanone or isopropyl alcohol for use.Can be wherein a kind of independent use, also can be that two or more mixes use.Preferred oxolane.Its consumption is counted with Radix Gentianae total glucosides and is not less than 1mL solvent/mg medicine.The drug level of the best after the optimization is 5-40mL organic solvent/mg medicine.
Among the present invention, the reaction temperature in the described phosphatide complexes preparation process can be 10 ℃～90 ℃; Response time can be 20min～8h; Remove organic solvent and can adopt drying under reduced pressure or lyophilization; Atent solvent can be selected dichloromethane, chloroform, ethyl acetate or oxolane for use, can be wherein a kind of independent use, also can be that two or more mixes use.Preferred chloroform.
Among the present invention, described Radix Gentianae total glucosides phosphatide complexes can further be made dosage forms such as granule, capsule, tablet, pill by adding suitable adjuvant.Affiliated adjuvant can be selected from starch, dextrin, lactose, silicon dioxide, calcium hydrogen phosphate, cyclodextrin, microcrystalline Cellulose, sodium carboxymethyl cellulose, magnesium stearate, Pulvis Talci etc.
Positive beneficial effect of the present invention is: prepared Radix Gentianae total glucosides phosphatide complexes can significantly improve the fat-soluble of Radix Gentianae total glucosides, change its physicochemical property, strengthen it and penetrate biomembrane and enter sanguimotor ability, thereby significantly improve the Radix Gentianae total glucosides bioavailability.Simultaneously preparation technology simple, be suitable for suitability for industrialized production.
Below by solubility test, the test of Caco-2 cell traffic, animal organism availability evidence beneficial effect of the present invention and practicality.
One, the solubility test of Radix Gentianae total glucosides and Radix Gentianae total glucosides phosphatide complexes
After Radix Gentianae total glucosides and phospholipid form phosphatide complexes, fat-soluble obvious improvement.According to " 2005 editions two solubility test methods of Chinese pharmacopoeia are investigated the variation of gentiopicrin being made the solubility property in all kinds of solvents behind the phosphatide complexes, and the result is as shown in table 1.Wherein easily dissolving means that solute 1g can dissolve in solvent 1～10ml; Dissolving means that solute 1g can dissolve in solvent 10～30ml; Slightly soluble means that solute 1g can dissolve in solvent 100～1000ml; Almost insoluble, mean that solute 1g can not dissolve fully in solvent 10000ml.
Table 1 Radix Gentianae total glucosides and the Radix Gentianae total glucosides phosphatide complexes solubility property in different solvents relatively
The above results shows, the fat-soluble Radix Gentianae total glucosides that is significantly higher than of Radix Gentianae total glucosides phosphatide complexes.
Two, Radix Gentianae total glucosides is made the structure verification of phosphatide complexes:
Adopt the thing phase change after differential heat scan DSC and X-ray diffraction method research Radix Gentianae total glucosides are made phosphatide complexes, the result respectively as shown in Figure 1 and Figure 2.
Fig. 1 show form phosphatide complexes after, the endothermic peak of phospholipid disappears, the endothermic peak reach of Radix Gentianae total glucosides shows and makes that the thing of Radix Gentianae total glucosides changes mutually behind the phosphatide complexes.Fig. 2 show make phosphatide complexes after, the crystal diffraction peak of crude drug disappears, the crystal form of the medicine formation amorphous substance that changes.
Three, adopt the Caco-2 cell model to carry out the in-vitro evaluation of Radix Gentianae total glucosides phosphatide complexes permeable membrane performance, the result as shown in Figure 3.
The result shows and makes the performance that can significantly improve the Radix Gentianae total glucosides transmembrane transport behind the phosphatide complexes, can reach 56 times of crude drug.
Four, Radix Gentianae total glucosides, Radix Gentianae total glucosides phosphatide complexes and Radix Gentianae total glucosides phosphatide complexes oil solution rat bioavailability are investigated
Healthy male Sprague-Dawley (SD) rat, body weight 180-200g, test fasting in preceding 24 hours and can't help water, every group 6, irritating stomach respectively and give Radix Gentianae total glucosides aqueous solution and Radix Gentianae total glucosides phosphatide complexes suspension, is 80mg/kg in the gentiopicrin dosage, and the tail vein is got blood, the blood drug level of gentiopicrin calculates area AUC and relative bioavailability under the plasma concentration curve behind the mensuration administration different time.Blood drug level-time graph is seen Fig. 4.Rat oral gavage gives the AUC behind Radix Gentianae total glucosides aqueous solution and the Radix Gentianae total glucosides phosphatide complexes suspension
0-∞Be respectively 6.27 ± 2.12 μ gmL
-1H and 23.38 ± 10.67 μ gmL
-1H.The result shows, makes the bioavailability that can significantly improve gentiopicrin behind the phosphatide complexes, and its relative bioavailability is 372.65%.
Description of drawings
The DSC figure of Fig. 1 Radix Gentianae total glucosides phosphatide complexes,
Wherein 1 is the Radix Gentianae total glucosides crude drug; 2 is phospholipid; 3 is Radix Gentianae total glucosides and phospholipid physical mixture;
4 is the Radix Gentianae total glucosides phosphatide complexes.
The X-ray diffractogram of Fig. 2 Radix Gentianae total glucosides phosphatide complexes,
Wherein 1 is the Radix Gentianae total glucosides crude drug; 2 is phospholipid; 3 is the Radix Gentianae total glucosides phosphatide complexes;
4 is Radix Gentianae total glucosides and phospholipid physical mixture.
Fig. 3 Radix Gentianae total glucosides phosphatide complexes Caco-2 cell traffic result.
Drug-time curve in the body of rat behind Fig. 4 Radix Gentianae total glucosides and the Radix Gentianae total glucosides phosphatide complexes gastric infusion.
The specific embodiment
Mode below by embodiment further specifies the present invention, but does not therefore limit the present invention among the described scope of embodiments.
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=13: 1)
Take by weighing Radix Gentianae total glucosides 450mg and soybean phospholipid 50mg places conical flask, add the 45mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent dark brown yellow solution, there is the minute quantity medicine to separate out, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=6: 1)
Take by weighing Radix Gentianae total glucosides 800mg and soybean phospholipid 200mg places conical flask, add the 80mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent dark brown yellow solution, the decompressing and extracting organic solvent adds an amount of ethyl acetate, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=2: 1)
Take by weighing Radix Gentianae total glucosides 600mg and soybean phospholipid 400mg places conical flask, add the 60mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of dichloromethane, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=1: 1)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of oxolane, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=1: 2)
Take by weighing Radix Gentianae total glucosides 245mg and soybean phospholipid 755mg places conical flask, add the 24.5mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 6
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=1: 4)
Take by weighing Radix Gentianae total glucosides 139mg and soybean phospholipid 861mg places conical flask, add the 14mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 7
Radix Gentianae total glucosides phosphatide complexes (medicine: fat=1: 10)
Take by weighing Radix Gentianae total glucosides 60mg and soybean phospholipid 940mg places conical flask, add the 6mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 8
The Radix Gentianae total glucosides phosphatide complexes
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL oxolane, in 80 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 9
The Radix Gentianae total glucosides phosphatide complexes
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL oxolane, in 40 ℃ of stirred in water bath 30min, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
The Radix Gentianae total glucosides phosphatide complexes
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL oxolane, in 40 ℃ of stirred in water bath 12h, form transparent light brown yellow solution, color wants dark than mixing time is short, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 11
The Radix Gentianae total glucosides phosphatide complexes
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 8mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent dark brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (egg yolk lecithin)
Take by weighing Radix Gentianae total glucosides 400mg and egg yolk lecithin 600mg places conical flask, add the 40mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 13
Radix Gentianae total glucosides phosphatide complexes (hydrogenated phospholipid)
Take by weighing Radix Gentianae total glucosides 400mg and hydrogenated phospholipid 600mg places conical flask, add the 40mL oxolane, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 14
Radix Gentianae total glucosides phosphatide complexes (ethyl acetate)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL ethyl acetate, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, the decompressing and extracting organic solvent adds an amount of chloroform, shake well, remove by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Radix Gentianae total glucosides phosphatide complexes (chloroform)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL chloroform, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, there is small amount of drug to separate out, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 16
Radix Gentianae total glucosides phosphatide complexes (acetone)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add 40mL acetone, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, there is medicine to separate out, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 17
Radix Gentianae total glucosides phosphatide complexes (dichloromethane)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add the 40mL dichloromethane, in 40 ℃ of stirred in water bath 3h, because the solvent highly volatile forms transparent dark brown yellow solution, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 18
Radix Gentianae total glucosides phosphatide complexes (methanol)
Take by weighing Radix Gentianae total glucosides 400mg and soybean phospholipid 600mg places conical flask, add 40mL methanol, in 40 ℃ of stirred in water bath 3h, form transparent light brown yellow solution, there is medicine to separate out, the decompressing and extracting organic solvent, add an amount of chloroform, shake well removes by filter precipitation, the filtrate drying promptly gets the Radix Gentianae total glucosides phosphatide complexes.
Embodiment 19
Radix Gentianae total glucosides phosphatide complexes tablet
Prescription is formed: Radix Gentianae total glucosides phosphatide complexes: 0.5g (embodiment 5 methods make)
Technical process: the Radix Gentianae total glucosides phosphatide complexes is mixed a certain amount of micropowder silica gel, place mortar, porphyrize is crossed 80 eye mesh screens, and the powder of obtaining adds 0.5% magnesium stearate, tabletting, promptly.
Radix Gentianae total glucosides phosphatide complexes capsule
Prescription is formed: Radix Gentianae total glucosides phosphatide complexes: 0.5g (embodiment 5 methods make)
Technical process: the Radix Gentianae total glucosides phosphatide complexes is mixed a certain amount of starch place mortar, porphyrize is crossed 80 eye mesh screens, and the powder of obtaining is got the blank capsules shell, and is encapsulated, promptly.
Embodiment 21
Radix Gentianae total glucosides phosphatide complexes capsule
Prescription is formed: Radix Gentianae total glucosides phosphatide complexes: 0.5g (embodiment 5 methods make)
Technical process: the Radix Gentianae total glucosides phosphatide complexes is mixed a certain amount of dextrin place mortar, porphyrize is crossed 80 eye mesh screens, and the powder of obtaining is got the blank capsules shell, and is encapsulated, promptly.
Embodiment 21
Radix Gentianae total glucosides phosphatide complexes capsule
Prescription is formed: Radix Gentianae total glucosides phosphatide complexes: 0.5g (embodiment 5 methods make)
Technical process: the Radix Gentianae total glucosides phosphatide complexes is mixed a certain amount of sodium carboxymethyl cellulose place mortar, porphyrize is crossed 80 eye mesh screens, and the powder of obtaining is got the blank capsules shell, and is encapsulated, promptly.
Claims (10)
1. the phosphatide complexes of a Radix Gentianae total glucosides is characterized in that, is crude drug with the effective ingredient in Chinese Radix Gentianae total glucosides, adopts suitable method to make with phospholipid; Described Radix Gentianae total glucosides is a raw material with Radix Gentianae or gentiana macrophylla medicine, through extracting the water solublity effective site that obtains behind the purification, wherein adopt determined by ultraviolet spectrophotometry, be not less than 50% in the content of the Radix Gentianae total glucosides of gentiopicrin, adopt the Determination of gentiopicroside of high effective liquid chromatography for measuring to be not less than 20%; Described phospholipid is selected from natural phospholipid, synthetic phospholipid or natural phospholipid and mixes use with synthetic phospholipid.
2. by the described Radix Gentianae total glucosides phosphatide complexes of claim 1, it is characterized in that described natural phospholipid is soybean lecithin or Ovum Gallus domesticus Flavus lecithin or two kinds of mixing uses; Described synthetic phospholipid is that hydrogenated soy phosphatidyl choline, hydrogenated yolk lecithin, dipalmitoyl phosphatidyl choline, two palmityl PHOSPHATIDYL ETHANOLAMINE, distearoyl phosphatidylcholine or DSPE or two or more mixing are wherein used; Or one or more natural phospholipids mix use with one or more synthetic phospholipids.
3. by the described Radix Gentianae total glucosides phosphatide complexes of claim 1, it is characterized in that described natural phospholipid is a soybean lecithin.
4. the preparation method of the Radix Gentianae total glucosides phosphatide complexes of claim 1, it is characterized in that, get it filled thing and phospholipid is mixed in the organic solvent with certain molar ratio, after reacting certain hour at a certain temperature, organic solvent is removed in decompression or lyophilization, adds atent solvent again and separates the free Radix Gentianae total glucosides that does not form phosphatide complexes, remove atent solvent, promptly get phosphatide complexes.
5. by the preparation method of claim 4, it is characterized in that: wherein the mol ratio of Radix Gentianae total glucosides and phospholipid is 1: 10～15: 1.
6. press the preparation method of claim 4, it is characterized in that described organic solvent is normal hexane, oxolane, methanol, ethanol, cyclohexane extraction, dioxy cyclohexane extraction, dichloromethane, ethyl acetate, chloroform, ether, acetone, n-butyl alcohol, dioxy six alkane, butanone or isopropyl alcohol; Or wherein a kind of independent use or two or more mixing use.
7. by the preparation method of claim 4, it is characterized in that the consumption of described organic solvent is not less than 1mL solvent/mg medicine in Radix Gentianae total glucosides.
8. by the preparation method of claim 4, it is characterized in that described reaction temperature is 10 ℃～90 ℃, the response time is 20min～8h.
9. press the preparation method of claim 4, it is characterized in that, described is dichloromethane, chloroform, ethyl acetate or oxolane in order to the atent solvent that separates the free Radix Gentianae total glucosides do not form phosphatide complexes, or wherein a kind of independent use or two or more mix and use.
10. by the phosphatide complexes of the described Radix Gentianae total glucosides of claim 1, it is characterized in that described complex adds suitable adjuvant and makes granule, capsule, tablet, pill, enteric coated capsule or enteric coatel tablets.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102001169A CN102085376A (en) | 2009-12-08 | 2009-12-08 | Phospholipid complex of gentian total glucosides and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102001169A CN102085376A (en) | 2009-12-08 | 2009-12-08 | Phospholipid complex of gentian total glucosides and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102085376A true CN102085376A (en) | 2011-06-08 |
Family
ID=44097536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102001169A Pending CN102085376A (en) | 2009-12-08 | 2009-12-08 | Phospholipid complex of gentian total glucosides and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102085376A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106511275A (en) * | 2016-10-27 | 2017-03-22 | 中国人民解放军第四军医大学 | Amarogentin-phospholipid complex and preparation method thereof |
| CN109010844A (en) * | 2017-06-08 | 2018-12-18 | 沈阳药科大学 | One kind is according to Shandong for Buddhist nun's phosphatide complexes and preparation method thereof |
| CN115429812A (en) * | 2022-08-31 | 2022-12-06 | 深圳海王医药科技研究院有限公司 | Molnbupiravir phospholipid complex and preparation method thereof |
-
2009
- 2009-12-08 CN CN2009102001169A patent/CN102085376A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106511275A (en) * | 2016-10-27 | 2017-03-22 | 中国人民解放军第四军医大学 | Amarogentin-phospholipid complex and preparation method thereof |
| CN106511275B (en) * | 2016-10-27 | 2021-02-19 | 中国人民解放军第四军医大学 | Gentianoside-phospholipid complex and preparation method thereof |
| CN109010844A (en) * | 2017-06-08 | 2018-12-18 | 沈阳药科大学 | One kind is according to Shandong for Buddhist nun's phosphatide complexes and preparation method thereof |
| CN109010844B (en) * | 2017-06-08 | 2022-01-04 | 沈阳药科大学 | Ibrutinib phospholipid complex and preparation method thereof |
| CN115429812A (en) * | 2022-08-31 | 2022-12-06 | 深圳海王医药科技研究院有限公司 | Molnbupiravir phospholipid complex and preparation method thereof |
| CN115429812B (en) * | 2022-08-31 | 2023-11-17 | 深圳海王医药科技研究院有限公司 | Monnpiravir phospholipid complex and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1320926C (en) | Ginkgo leaf extract composition and its prepn | |
| KR101607445B1 (en) | Novel milk thistle extract, method for the production, and use | |
| CN100594898C (en) | Pharmaceutical composition of Silybin and preparation method thereof | |
| CN102107006A (en) | Coupling medicament for treating diabetes mellitus and medicinal application thereof | |
| CN101181282B (en) | Hydroxyl radical carthamin yellow carthamus A soft capsule with high bioavailability and preparation method thereof | |
| CN101637467A (en) | Herba epimedii aglycone or cyclo-herba epimedii aglycone phospholipid compound and preparation method thereof | |
| CN101095670B (en) | Luteolin phospholipid complexes and method for preparing the same and application thereof | |
| CN101530389B (en) | Ginsenoside Rg 3 and phospholipid complex and preparing method thereof | |
| CN107213467A (en) | A kind of preparation method of phospholipid complexes of curcumin | |
| CN101704838A (en) | Baicalein phospholipid complex and preparation method thereof | |
| CN107488162A (en) | A kind of bicyclic alcohol derivatives and its preparation and application | |
| CN101199508B (en) | Salvianic phenol acid or salt phospholipid compound and preparing method thereof | |
| CN102085376A (en) | Phospholipid complex of gentian total glucosides and preparation method thereof | |
| WO2008145064A1 (en) | The method for a sequoyitol-containing extract obtaining from the genus of trifolium, sobyean and ginkgo biloba and use thereof | |
| CN100477997C (en) | Hydrophobic formulation containing total notoginseng glycosides and phospholipid and preparation method thereof | |
| WO2011071194A1 (en) | SOLID DISPERSIONS CONTAINING 20-O-β-D-GLUCOPYRANOSYL-20(S)-PROTOPANAXADIOL | |
| CN102058642B (en) | Ginseng saponin extract and preparation method thereof | |
| CN100417378C (en) | Oridonin clathrate compound, and medicinal prepn. thereof | |
| CN1264509C (en) | Precursor liposome preparation containing silybum marianum extract and its preparing process | |
| CN101618222B (en) | Anethol trithione and phospholipid compound and preparation method thereof | |
| CN101524349B (en) | Phospholipids compound of bicyclo-ethanol and preparation method thereof | |
| CN104383547B (en) | Herba Saussureae Involueratae extract phosphatide complexes, oral disnitegration tablet and preparation method thereof | |
| CN101259100B (en) | Etoposide preparations and preparation thereof | |
| CN1311823C (en) | Indirubin phosphatide compound and its preparation method | |
| CN102085238A (en) | Lipid preparation containing radix gentianae totalglycoside-phospholipid complexes and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110608 |